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Introduction
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September 2018 - March 2021
May 2019 - present
September 2017 - present
Publications
Publications (65)
Background
Cardiac remodelling, a crucial aspect of heart failure, is commonly investigated in preclinical models by quantifying cardiomyocyte cross‐sectional area (CSA) and microvascular density (MVD) via histological methods, such as immunohistochemistry. To achieve this, optimized protocols are needed, and the species specificity is dependent on...
Regeneration of sensory axons after a burn injury depends on early keratinocyte responses regulated by the wound microenvironment.
Leukotriene B4 (LTB4) is a potent lipid chemoattractant driving inflammatory responses during host defense, allergy, autoimmune and metabolic diseases. Gradients of LTB4 orchestrate leukocyte recruitment and swarming to sites of tissue damage and infection. How LTB4 gradients form and spread in live tissues to regulate these processes remains large...
Keratinocytes of the mammalian skin provide not only mechanical protection for the tissues, but also transmit mechanical, chemical, and thermal stimuli from the external environment to the sensory nerve terminals. Sensory nerve fibers penetrate the epidermal basement membrane and function in the tight intercellular space among keratinocytes. Here w...
Keratinocytes of the mammalian skin provide not only mechanical protection for the tissues, but also transmit mechanical, chemical, and thermal stimuli from the external environment to the sensory nerve terminals. Sensory nerve fibers penetrate the epidermal basement membrane and function in the tight intercellular space among keratinocytes. Here w...
ATP is an important energy metabolite and allosteric signal in health and disease. ATP-interacting proteins, such as P2 receptors, control inflammation, cell death, migration, and wound healing. However, identification of allosteric ATP sites remains challenging, and our current inventory of ATP-controlled pathways is likely incomplete. Here, we de...
Introduction:
The etiology of radiation-induced erectile dysfunction (ED) is complex and multifactorial, and it appears to be mainly atherogenic.
Aim:
To focus on vascular aspects of radiation-induced ED and to elucidate whether the protective effects of sildenafil are mediated by attenuation of oxidative stress and apoptosis in the endothelial...
Quantitative aspects of extracellular H2O2 signaling in animals, such as its spatiotemporal dynamics within tissues, remain little understood. Here we detail an optimized, experimental setup for measuring the dynamics and physiological consequences of extracellular H2O2 application to live tissues by intravital biosensor imaging in zebrafish larvae...
Hydrogen peroxide (H2O2) is an important signaling intermediate with various regulatory and effector functions. Despite its significance, the subcellular organization of H2O2 signals is poorly understood. Introducing novel techniques for the intracellular detection of H2O2 would be essential for a more complete understanding of its role in cellular...
Studying early immune responses to organ damage in situ requires animal models amenable to intravital imaging. Here, we used transparent zebrafish larvae, a powerful animal model for innate immunity, to measure leukocyte recruitment to damaged livers. Bath application of metronidazole (Mtz) to fish expressing nitroreductase (NTR) under a liver-spec...
Supplementary material. Supplementary Figure 1. Nox4 and Duox1 specific western blots on tissue samples of knockout animals A) isolated kidney was mechanically dissected in ice cold RIPA lysis buffer using a Turrax disperser. Insoluble fraction was centrifuged and the soluble fraction was processed for Nox4 western blot on 10% SDS polyacrylamide ge...
Collagen IV is a major component of the basement membrane in epithelial tissues. The NC1 domains of collagen IV protomers are covalently linked together through sulfilimine bonds, the formation of which is catalyzed by peroxidasin. Although hydrogen peroxide is essential for this reaction, the exact source of the oxidant remains elusive. Members of...
The p22phox protein is an essential component of the phagocytic- and inner ear NADPH oxidases but its relationship to other Nox proteins is less clear. We have studied the role of p22phox in the TGF-β1-stimulated H2O2 production of primary human and murine fibroblasts. TGF-β1 induced H2O2 release of the examined cells, and the response was dependen...
Epithelial injury induces rapid recruitment of antimicrobial leukocytes to the wound site. In zebrafish larvae, activation of the epithelial NADPH oxidase Duox at the wound margin is required early during this response. Before injury, leukocytes are near the vascular region, that is, ∼100–300 μm away from the injury site. How Duox establishes long-...
Most research in nuclear mechanotransduction has focused on the nuclear lamina and lamin binding proteins. These structures provide mechanical stability to the nucleus, establish a link between the cytoskeleton and chromatin, and can transmit mechanical signals. At the same time, mechanical perturbations to the nucleus also affect its phospholipid...
The ER-mitochondrial interface is central to calcium signaling, organellar dynamics, and lipid biosynthesis. The ER and mitochondrial membranes also host sources and targets of reactive oxygen species (ROS), but their local dynamics and relevance remained elusive since measurement and perturbation of ROS at the organellar interface has proven diffi...
Tissue damage activates cytosolic phospholipase A2 (cPLA2), releasing arachidonic acid (AA), which is oxidized to proinflammatory eicosanoids by 5-lipoxygenase (5-LOX) on the nuclear envelope. How tissue damage is sensed to activate cPLA2 is unknown. We investigated this by live imaging in wounded zebrafish larvae, where damage of the fin tissue ca...
The intrinsic near-infrared photoluminescence (fluorescence) of single-walled carbon nanotubes exhibits unique photostability, narrow bandwidth, penetration through biological media, environmental sensitivity, and both chromatic variety and range. Biomedical applications exploiting this large family of fluorophores will require the spectral and spa...
The cell nucleus is becoming increasingly recognized as a mechanosensitive organelle. Most research on nuclear mechanosignaling focuses on the nuclear lamina and coupled actin structures. In this commentary, we discuss the possibility that the nuclear membrane senses and transduces mechanical signals similar to the plasma membrane. We briefly summa...
The intrinsic near-infrared photoluminescence (fluorescence) of single-walled carbon nanotubes exhibits unique photostability, narrow bandwidth, penetration through biological media, environmental sensitivity, and both chromatic variety and range. Biomedical applications exploiting this large family of fluorophores will require the spectral and spa...
Efficient wound healing requires the coordinated responses of various cell types within an injured tissue. To react to the presence of a wound, cells have to first detect it. Judging from their initial biochemical and morphological responses, many cells including leukocytes, epithelial cells, and endothelial cells detect wounds from over hundreds o...
The endoplasmic reticulum (ER) is a metabolically active organelle, which has a central role in proteostasis by translating, modifying, folding and occasionally degrading secretory and membrane proteins. The lumen of the ER represents a separate compartment of the eukaryotic cell, with a characteristic proteome and metabolome. Although the redox me...
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Osmotic cues from the environment mediate rapid detection of epithelial breaches by leukocytes in larval zebrafish tail fins. Using intravital luminescence and fluorescence microscopy, we now show that osmolarity differences between the interstitial fluid and the external environment trigger ATP release at tail fin wounds to initiate rapid wound cl...
How tissue damage is detected to induce inflammatory responses is unclear. Most studies have focused on damage signals released by cell breakage and necrosis. Whether tissues use other cues in addition to cell lysis to detect that they are damaged is unknown. We find that osmolarity differences between interstitial fluid and the external environmen...
H2O2 is a relatively stable, rapidly diffusing reactive oxygen species that has been recently implicated as a mediator of leukocyte recruitment to epithelial wounds and transformed cells in zebrafish. Whether H2O2 activates the innate immune response by acting as a bona fide chemoattractant, enhancing chemoattractant sensing, or triggering producti...
Multiple interactions between Ca2+-signalling and reactive oxygen species (ROS) production are thought to exist and be of both physiological and pathophysiological relevance. However, until recently, the study of ROS in the context of Ca2+-signalling has been hampered by ROS probes limited in both specificity and targeting. To measure ROS in discre...
Aims:
Hydrogen peroxide (H2O2) is an emerging signaling molecule with diverse regulatory functions. Despite its significance, the spatial and temporal organization of H2O2 signals within cells is basically unknown. Our limited knowledge about H2O2 signals is largely due to the lack of appropriate techniques for measuring intracellular H2O2. The ai...
Morphology of the mitochondria of RNA-transfected H295R cells. The cells were transfected with control RNA (A), Mfn1 siRNA (B) or OPA1 siRNA (C) on the day following plating (day 2) and with mitochondrially targeted GFP on day 3. Confocal microscopy was performed on day 4. The framed areas are shown in the right-hand column; zoom: 4×. Optical slice...
Morphology of the mitochondria of RNA-transfected HeLa cells. The cells were transfected with control RNA (A), Mfn1 siRNA (B) or OPA1 siRNA (C) on the day following plating (day 2) and with mitochondrially targeted GFP on day 3. Confocal microscopy was performed on day 5. The framed areas are shown in the right-hand column; zoom: 4×. Optical slice...
Mitochondrial membrane potential of RNA-transfected HeLa cells. Transfection with control RNA, Mfn1 or OPA1 siRNA was performed on the day following plating. Three days later Ψm was estimated applying TMRM in H295R cells and TMRE or JC-1 in HeLa cells, respectively. TMRM and TMRE fluorescence or JC-1 ratio (red/green) over the mitochondrial region...
Morphometry of the mitochondria of RNA-transfected cells. For the experimental protocol see the legend of Figure S1 (H295R) or 2 (HeLa). The histograms show the length and circularity of mitochondria in H295R cells (A and B, resp.) and in HeLa cells (C and D, resp.). Analysis was performed with ImageJ 1.6.0, as suggested [71].
(TIF)
Pharmacological characterization of the Ca2+ transport mechanism in depolarized mitochondria. H295R cells (A) or HeLa cells (B) were transfected with OPA1 siRNA 1 day after plating (day 2). On day 5 the cells were loaded with Rhod-2 AM, permeabilized and superfused with a cytosol-like medium. Ψm was dissipated (see legend of Figure 5) and then [Ca2...
Significance of differences for the experiments shown in Figure S5. C: control, RR: Ruthenium Red, CG: CGP-37157, Cy: cyclosporine A.
(DOC)
The dynamin-related GTPase protein OPA1, localized in the intermembrane space and tethered to the inner membrane of mitochondria, participates in the fusion of these organelles. Its mutation is the most prevalent cause of Autosomal Dominant Optic Atrophy. OPA1 controls the diameter of the junctions between the boundary part of the inner membrane an...
Hydrogen peroxide (H(2)O(2)) has important messenger and effector functions in the plant and animal kingdom. Phagocytes produce H(2)O(2) to kill pathogens, and epithelial cells of large airways have also been reported to produce H(2)O(2) for signaling and host defense purposes. In this report, we show for the first time that urothelial cells produc...
Formation of intra- and intermolecular disulfide bonds is an essential step in the synthesis of secretory proteins. In eukaryotic cells, this process occurs in the endoplasmic reticulum (ER) and requires an oxidative environment with the action of several chaperones and folding catalysts. During protein folding, Ero1p oxidizes protein disulfide iso...
Neonatal severe hyperparathyroidism (NSHPT) is induced by inactivating mutations of human calcium-sensing receptor (CaSR). Only three heterozygous de novo inactivating mutations of CaSR causing NSHPT have been described. We report the case of a now 11-year-old boy with NSHPT and we characterize a novel inactivating mutation along with the results o...
Cortactin is an SH3 domain-containing protein that contributes to the formation of dynamic cortical actin-associated structures, such as lamellipodia and membrane ruffles. It was originally identified as a substrate for the protein kinase Src; however, the role of tyrosine phosphorylation in the translocation of cortactin to the cell periphery and...
Cortactin is an SH3 domain-containing protein that contributes to the formation of dynamic cortical actin-associated structures, such as lamellipodia and membrane ruffles. Here we show that expression of either the GFP-tagged N-terminal or the C-teminal halves of cortactin inhibits significantly the spreading of COS7 cells on fibronectin. Introduci...
Different polymorphisms have been described in the minimal promoter region (MPR) of the interferon-gamma receptor 1 (IFNGR1), a molecule that plays a critical role in mycobacterial control. We sequenced the IFNGR1 MPR from African American, Caucasian and Korean controls, and from mycobacteria-infected patients. Six different single nucleotide polym...
